Search results for: diatomic molecules

Authors: S. Pradhan, D. Pradhan, G. Tripathy

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Anti-estrogen treatment resistant is a noteworthy reason for disease relapse and mortality in estrogen receptor alpha (ERα)- positive breast cancers. Tamoxifen or estrogen withdrawal increases the dependance of breast malignancy cells on INT3 signaling. Here, we researched the contribution of Quercetin and INT3 signaling in endocrine resistant breast cancer cells. Methods: We utilized two models of endocrine therapies resistant (ETR-) breast cancer: tamoxifen-resistant (TamR) and long term estrogen-deprived (LTED) MCF7 cells. We assessed the migratory and invasive limit of these cells by Transwell assay. Expression of epithelial to mesenchymal transition (EMT) controllers and in addition INT3 receptors and targets were assessed by real-time PCR and western blot analysis. Besides, we tried in vitro anti-Quercetin monoclonal antibodies (mAbs) and gamma secretase inhibitors (GSIs) as potential EMT reversal therapeutic agents. At last, we created stable Quercetin over expessing MCF7 cells and assessed their EMT features and response to tamoxifen. Results:We found that ETR cells acquired an epithelial to mesenchymal transition (EMT) phenotype and showed expanded levels of Quercetin and INT3 targets. Interestingly, we detected higher level of INT3 however lower levels of INT31 and INT32 proposing a switch to targeting through distinctive INT3 receptors after obtaining of resistance. Anti-Quercetin monoclonal antibodies and the GSI PF03084014 were effective in obstructing the Quercetin/INT3 axis and in part inhibiting the EMT process. As a consequence of this, cell migration and invasion were weakened and the stem cell like population was considerably decreased. Genetic hushing of Quercetin and INT3 prompted proportionate impacts. Finally, stable overexpression of Quercetin was adequate to make MCF7 lethargic to tamoxifen by INT3 activation. Conclusions: ETR cells express abnormal amounts of Quercetin and INT3, whose actuation eventually drives invasive conduct. Anti-Quercetin mAbs and GSI PF03084014 lessen expression of EMT molecules decreasing cellular invasiveness. Quercetin overexpression instigates tamoxifen resistance connected to obtaining of EMT phenotype. Our discovering propose that focusing on Quercetin and/or INT3 warrants further clinical assessment as substantial therapeutic methodologies in endocrine-resistant breast cancer.

Keywords: quercetin, INT3, mesenchymal transition, MCF7 breast cancer cells

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Authors: Jignasha Derasari, Patel Krishna M, Modi Jignasa G.

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Chemical stability of pharmaceutical molecules is a matter of great concern as it affects the safety and efficacy of the drug product.Stability testing data provides the basis to understand how the quality of a drug substance and drug product changes with time under the influence of various environmental factors. Besides this, it also helps in selecting proper formulation and package as well as providing proper storage conditions and shelf life, which is essential for regulatory documentation. The ICH guideline states that stress testing is intended to identify the likely degradation products which further help in determination of the intrinsic stability of the molecule and establishing degradation pathways, and to validate the stability indicating procedures. A simple, accurate and precise stability indicating RP- HPLC method was developed and validated for simultaneous estimation of Amiloride Hydrochloride and Furosemide in tablet dosage form. Separation was achieved on an Phenomenexluna ODS C18 (250 mm × 4.6 mm i.d., 5 µm particle size) by using a mobile phase consisting of Ortho phosphoric acid: Acetonitrile (50:50 %v/v) at a flow rate of 1.0 ml/min (pH 3.5 adjusted with 0.1 % TEA in Water) isocratic pump mode, Injection volume 20 µl and wavelength of detection was kept at 283 nm. Retention time for Amiloride Hydrochloride and Furosemide was 1.810 min and 4.269 min respectively. Linearity of the proposed method was obtained in the range of 40-60 µg/ml and 320-480 µg/ml and Correlation coefficient was 0.999 and 0.998 for Amiloride hydrochloride and Furosemide, respectively. Forced degradation study was carried out on combined dosage form with various stress conditions like hydrolysis (acid and base hydrolysis), oxidative and thermal conditions as per ICH guideline Q2 (R1). The RP- HPLC method has shown an adequate separation for Amiloride hydrochloride and Furosemide from its degradation products. Proposed method was validated as per ICH guidelines for specificity, linearity, accuracy; precision and robustness for estimation of Amiloride hydrochloride and Furosemide in commercially available tablet dosage form and results were found to be satisfactory and significant. The developed and validated stability indicating RP-HPLC method can be used successfully for marketed formulations. Forced degradation studies help in generating degradants in much shorter span of time, mostly a few weeks can be used to develop the stability indicating method which can be applied later for the analysis of samples generated from accelerated and long term stability studies. Further, kinetic study was also performed for different forced degradation parameters of the same combination, which help in determining order of reaction.

Keywords: amiloride hydrochloride, furosemide, kinetic study, stability indicating RP-HPLC method validation

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Authors: Elena Maria Scalisi

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The increasing production and the use of TiO₂ nanoparticles (NPs) have inevitably led to their release into the environment, thereby posing a threat to organisms and also for human. Human exposure to TiO₂-NPs may occur during both manufacturing and use. TiO₂-NPs are common in consumer products for dermal application, toothpaste, food colorants, and nutritional supplements, then oral exposure may occur during use of such products. Into the body, TiO₂-NPs thanks to their small size (<100 nm), can, through testicular blood barrier inducing effect on testis and then on male reproductive health. The nanoscale size of TiO₂ increase the surface-to-volume ratio making them more reactive in a cell, then TiO₂ NPs increase their ability to produce reactive oxygen species (ROS). In male germ cells, ROS may have important implications in maintaining the normal functions of mature spermatozoa at physiological levels, moreover, in spermatozoa they are important signaling molecules for their hyperactivation and acrosome reaction. Nevertheless, an excess of ROS by external inputs such as NPs can increased the oxidative stress (OS), which results in damage DNA and apoptosis. The aim of our study has been investigate the impact of TiO₂ NPs on human spermatozoa, evaluating DNA damage and the expression of proteins involved in cell stress. According WHO guidelines 2021, we have exposed human spermatozoa in vitro to TiO₂ NP at concentrations 50 ppm, 100 ppm, 250 ppm, and 500 ppm for 1 hour (at 37°C and CO₂ at 5%). DNA damage was evaluated by Sperm Chromatin Dispersion Test (SCD) and TUNEL assay; moreover, we have evaluated the expression of biomarkers of oxidative stress like Heat Shock Protein 70 (HSP70) and Metallothioneins (MTs). Also, sperm parameters as motility viability have been evaluated. Our results not report a significant reduction in motility of spermatozoa at the end of the exposure. On the contrary, the progressive motility was increased at the highest concentration (500 ppm) and was statistically significant compared to control (p <0.05). Also, viability was not changed by exposure to TiO₂-NPs (p <0.05). However, increased DNA damage was observed at all concentrations, and the TUNEL assay highlighted the presence of single strand breaks in the DNA. The spermatozoa responded to the presence of TiO₂-NPs with the expression of Hsp70, which have a protective function because they allow the maintenance of cellular homeostasis in stressful/ lethal conditions. A positivity for MTs was observed mainly for the concentration of 4 mg/L. Although the biological and physiological function of the metallothionein (MTs) in the male genital organs is unclear, our results highlighted that the MTs expressed by spermatozoa maintain their biological role of detoxification from metals. Our results can give additional information to the data in the literature on the toxicity of TiO₂-NPs and reproduction.

Keywords: human spermatozoa, DNA damage, TiO₂-NPs, biomarkers

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Authors: Maki Mizogami, Hironori Tsuchiya, Yoshiroh Hayabuchi, Kenji Shigemi

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Since drugs exhibit significant structure-dependent differences in activity and toxicity, their differentiation based on the mechanism of action should have implications for comparative drug efficacy and safety. We aimed to differentiate drug stereoisomers by their stereostructure-selective membrane interactions underlying pharmacological and toxicological effects. Biomimetic lipid bilayer membranes were prepared with phospholipids and sterols (either cholesterol or epicholesterol) to mimic the lipid compositions of neuronal and cardiomyocyte membranes and to provide these membranes with the chirality. The membrane preparations were treated with different classes of stereoisomers at clinically- and pharmacologically-relevant concentrations (25-200 μM), followed by measuring fluorescence polarization to determine the membrane interactivity of drugs to change the physicochemical property of membranes. All the tested drugs acted on lipid bilayers to increase or decrease the membrane fluidity. Drug stereoisomers could not be differentiated when interacting with the membranes consisting of phospholipids alone. However, they stereostructure-selectively interacted with neuro-mimetic and cardio-mimetic membranes containing 40 mol% cholesterol ((3β)-cholest-5-en-3-ol) to show the relative potencies being local anesthetic R(+)-bupivacaine > rac-bupivacaine > S(‒)-bupivacaine, α2-adrenergic agonistic D-medetomidine > rac-medetomidine > L-medetomidine, β-adrenergic antagonistic R(+)-propranolol > rac-propranolol > S(–)-propranolol, NMDA receptor antagonistic S(+)-ketamine > rac-ketamine, analgesic monoterpenoid (+)-menthol > (‒)-menthol, non-steroidal anti-inflammatory S(+)-ibuprofen > rac-ibuprofen > R(‒)-ibuprofen, and bioactive flavonoid (+)-epicatechin > (‒)-epicatechin. All of the order of membrane interactivity were correlated to those of beneficial and adverse effects of the tested stereoisomers. In contrast, the membranes prepared with epicholesterol ((3α)-chotest-5-en-3-ol), an epimeric form of cholesterol, reversed the rank order of membrane interactivity to be S(‒)-enantiomeric > racemic > R(+)-enantiomeric bupivacaine, L-enantiomeric > racemic > D-enantiomeric medetomidine, S(–)-enantiomeric > racemic > R(+)-enantiomeric propranolol, racemic > S(+)-enantiomeric ketamine, (‒)-enantiomeric > (+)-enantiomeric menthol, R(‒)-enantiomeric > racemic > S(+)-enantiomeric ibuprofen, and (‒)-enantiomeric > (+)-enantiomeric epicatechin. The opposite configuration allows drug molecules to interact with chiral sterol membranes enantiomer-selectively. From the comparative results, it is speculated that a 3β-hydroxyl group in cholesterol is responsible for the enantioselective interactions of drugs. In conclusion, the differentiation of drug stereoisomers by their stereostructure-selective membrane interactions would be useful for designing and predicting drugs with higher activity and/or lower toxicity.

Keywords: chiral membrane, differentiation, drug stereoisomer, enantioselective membrane interaction

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Authors: Y. Muto, S. Araki, H. Yamamoto

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The separation of oxygen is one key technology to improve the efficiency and to reduce the cost for the processed of the partial oxidation of the methane and the condensation of the carbon dioxide. Particularly, carbon dioxide at high concentration would be obtained by the combustion using pure oxygen separated from air. However, the oxygen separation process occupied the large part of energy consumption. Therefore, it is considered that the membrane technologies enable to separation at lower cost and lower energy consumption than conventional methods. In this study, it is examined that the separation of oxygen using membranes of mixed conductors. Oxygen permeation through the membrane is occurred by the following three processes. At first, the oxygen molecules dissociate into oxygen ion at feed side of the membrane, subsequently, oxygen ions diffuse in the membrane. Finally, oxygen ions recombine to form the oxygen molecule. Therefore, it is expected that the membrane of thickness and material, or catalysts of the dissociation and recombination affect the membrane performance. However, there is little article about catalysts for the dissociation and recombination. We confirmed the performance of La0.6Sr0.4Co1.0O3-δ (LSC) based catalyst which was commonly used as the dissociation and recombination. It is known that the adsorbed amount of oxygen increase with the increase of doped Fe content in B site of LSC. We prepared the catalysts of La0.1Sr0.9Co0.9Fe0.1O3-δ(C9F1), La0.1Sr0.9Co0.5Fe0.5O3-δ(C5F5) and La0.1Sr0.9Co0.3Fe0.7O3-δ(C7F3). Also, we used Pr2NiO4 type mixed conductor as a membrane material. (Pr0.9La0.1)2(Ni0.74Cu0.21Ga0.05)O4+δ(PLNCG) shows the high oxygen permeability and the stability against carbon dioxide. Oxygen permeation experiments were carried out using a homemade apparatus at 850 -975 °C. The membrane was sealed with Pyrex glass at both end of the outside dense alumina tubes. To measure the oxygen permeation rate, air was fed to the film side at 50 ml min-1, helium as the sweep gas and reference gas was fed at 20 ml min-1. The flow rates of the sweep gas and the gas permeated through the membrane were measured using flow meter and the gas concentrations were determined using a gas chromatograph. Then, the permeance of the oxygen was determined using the flow rate and the concentration of the gas on the permeate side of the membrane. The increase of oxygen permeation was observed with increasing temperature. It is considered that this is due to the catalytic activities are increased with increasing temperature. Another reason is the increase of oxygen diffusivity in the bulk of membrane. The oxygen permeation rate is improved by using catalyst of LSC or LSCF. The oxygen permeation rate of membrane with LSCF showed higher than that of membrane with LSC. Furthermore, in LSCF catalysts, oxygen permeation rate increased with the increase of the doped amount of Fe. It is considered that this is caused by the increased of adsorbed amount of oxygen.

Keywords: membrane separation, oxygen permeation, K2NiF4-type structure, mixed conductor

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Authors: Rasha Al-Saedi, Anthony Meijer

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The progress of new porous materials has increased rapidly over the past decade for use in applications such as catalysis, gas storage and removal of environmentally unfriendly species due to their high surface area and high thermal stability. In this work, a theoretical study of the zirconium-based metal organic framework (MOFs) were examined in order to determine their potential for gas adsorption of various guest molecules: CO2, N2, CH4 and H2. The zirconium cluster consists of an inner Zr6O4(OH)4 core in which the triangular faces of the Zr6- octahedron are alternatively capped by O and OH groups which bound to nine formate groups and three benzoate groups linkers. General formula is [Zr(μ-O)4(μ-OH)4(HCOO)9((phyO2C)3X))] where X= CH2OH, CH2NH2, CH2CONH2, n(NH2); (n = 1-3). Three types of adsorption sites on the Zr metal center have been studied, named according to capped chemical groups as the ‘−O site’; the H of (μ-OH) site removed and added to (μ-O) site, ‘–OH site’; (μ-OH) site removed, the ‘void site’ where H2O molecule removed; (μ-OH) from one site and H from other (μ-OH) site, in addition to no defect versions. A series of investigations have been performed aiming to address this important issue. First, density functional theory DFT-B3LYP method with 6-311G(d,p) basis set was employed using Gaussian 09 package in order to evaluate the gas adsorption performance of missing-linker defects in zirconium cluster. Next, study the gas adsorption behaviour on different functionalised zirconium clusters. Those functional groups as mentioned above include: amines, alcohol, amide, in comparison with non-substitution clusters. Then, dispersion-corrected density functional theory (DFT-D) calculations were performed to further understand the enhanced gas binding on zirconium clusters. Finally, study the water effect on CO2 and N2 adsorption. The small functionalized Zr clusters were found to result in good CO2 adsorption over N2, CH4, and H2 due to the quadrupole moment of CO2 while N2, CH4 and H2 weakly polar or non-polar. The adsorption efficiency was determined using the dispersion method where the adsorption binding improved as most of the interactions, for example, van der Waals interactions are missing with the conventional DFT method. The calculated gas binding strengths on the no defect site are higher than those on the −O site, −OH site and the void site, this difference is especially notable for CO2. It has been stated that the enhanced affinity of CO2 of no defect versions is most likely due to the electrostatic interactions between the negatively charged O of CO2 and the positively charged H of (μ-OH) metal site. The uptake of the gas molecule does not enhance in presence of water as the latter binds to Zr clusters more strongly than gas species which attributed to the competition on adsorption sites.

Keywords: density functional theory, gas adsorption, metal- organic frameworks, molecular simulation, porous materials, theoretical chemistry

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Authors: Luminita Marin, Dalila Belei, Carmen Dumea

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Aggregation induced emission (AIE) is an intriguing optical phenomenon recently evidenced by Tang and his co-workers, for which aggregation works constructively in the improving of light emission. The AIE challenging phenomenon is quite opposite to the notorious aggregation caused quenching (ACQ) of light emission in the condensed phase, and comes in line with requirements of photonic and optoelectronic devices which need solid state emissive substrates. This paper reports a series of ten new aggregation induced emission (AIE) low molecular weight compounds based on triazole and pyridine-N-oxide heterocyclic units bonded by short flexible chains, obtained by a „click” chemistry reaction. The compounds present extremely weak luminescence in solution but strong light emission in solid state. To distinguish the influence of the crystallinity degree on the emission efficiency, the photophysical properties were explored by UV-vis and photoluminescence spectroscopy in solution, water suspension, amorphous and crystalline films. On the other hand, the compound morphology of the up mentioned states was monitored by dynamic light scattering, scanning electron microscopy, atomic force microscopy and polarized light microscopy methods. To further understand the structural design – photophysical properties relationship, single crystal X-ray diffraction on some understudy compounds was performed too. The UV-vis absorption spectra of the triazole water suspensions indicated a typical behaviour for nanoparticle formation, while the photoluminescence spectra revealed an emission intensity enhancement up to 921-fold higher of the crystalline films compared to solutions, clearly indicating an AIE behaviour. The compounds have the tendency to aggregate forming nano- and micro- crystals in shape of rose-like and fibres. The crystals integrity is kept due to the strong lateral intermolecular forces, while the absence of face-to-face forces explains the enhanced luminescence in crystalline state, in which the intramolecular rotations are restricted. The studied flexible triazoles draw attention to a new structural design in which small biologically friendly luminophore units are linked together by small flexible chains. This design enlarges the variety of the AIE luminogens to the flexible molecules, guiding further efforts in development of new AIE structures for appropriate applications, the biological ones being especially envisaged.

Keywords: aggregation induced emission, pyridine-N-oxide, triazole

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Authors: Srinivas Bathini, Duraichelvan Raju, Simona Badilescu, Muthukumaran Packirisamy

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A bio-sensing method, based on the plasmonic property of gold nano-islands, has been developed for detection of exosomes in a clinical setting. The position of the gold plasmon band in the UV-Visible spectrum depends on the size and shape of gold nanoparticles as well as on the surrounding environment. By adsorbing various chemical entities, or binding them, the gold plasmon band will shift toward longer wavelengths and the shift is proportional to the concentration. Exosomes transport cargoes of molecules and genetic materials to proximal and distal cells. Presently, the standard method for their isolation and quantification from body fluids is by ultracentrifugation, not a practical method to be implemented in a clinical setting. Thus, a versatile and cutting-edge platform is required to selectively detect and isolate exosomes for further analysis at clinical level. The new sensing protocol, instead of antibodies, makes use of a specially synthesized polypeptide (Vn96), to capture and quantify the exosomes from different media, by binding the heat shock proteins from exosomes. The protocol has been established and optimized by using a glass substrate, in order to facilitate the next stage, namely the transfer of the protocol to a microfluidic environment. After each step of the protocol, the UV-Vis spectrum was recorded and the position of gold Localized Surface Plasmon Resonance (LSPR) band was measured. The sensing process was modelled, taking into account the characteristics of the nano-island structure, prepared by thermal convection and annealing. The optimal molar ratios of the most important chemical entities, involved in the detection of exosomes were calculated as well. Indeed, it was found that the results of the sensing process depend on the two major steps: the molar ratios of streptavidin to biotin-PEG-Vn96 and, the final step, the capture of exosomes by the biotin-PEG-Vn96 complex. The microfluidic device designed for sensing of exosomes consists of a glass substrate, sealed by a PDMS layer that contains the channel and a collecting chamber. In the device, the solutions of linker, cross-linker, etc., are pumped over the gold nano-islands and an Ocean Optics spectrometer is used to measure the position of the Au plasmon band at each step of the sensing. The experiments have shown that the shift of the Au LSPR band is proportional to the concentration of exosomes and, thereby, exosomes can be accurately quantified. An important advantage of the method is the ability to discriminate between exosomes having different origins.

Keywords: exosomes, gold nano-islands, microfluidics, plasmonic biosensing

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Authors: Chrislaura Carmo, Luca Deiana, Mafalda Laranjo, Abilio Sobral, Armando Cordova

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Photodynamic therapy (PDT) is currently used for the treatment of malignancies and premalignant tumors. It is based on the capture of a photosensitizing molecule (PS) which, when excited by light at a certain wavelength, reacts with oxygen and generates oxidizing species (radicals, singlet oxygen, triplet species) in target tissues, leading to cell death. BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indaceno) derivatives are emerging as important candidates for photosensitizer in photodynamic therapy of cancer cells due to their high triplet quantum yield. Today these dyes are relevant molecules in photovoltaic materials and fluorescent sensors. In this study, it will be demonstrated the possibility that BODIPY can be covalently linked to thioglycolic acid through the click reaction. Thiol−ene click chemistry has become a powerful synthesis method in materials science and surface modification. The design of biobased allyl-terminated precursors with high renewable carbon content for the construction of the thiol-ene polymer networks is essential for sustainable development and green chemistry. The work aims to synthesize the BODIPY (10-(4-(allyloxy) phenyl)-2,8-diethyl-5,5-difluoro-1,3,7,9-tetramethyl-5H-dipyrrolo[1,2-c:2',1'-f] [1,3,2] diazaborinin-4-ium-5-uide) and to click reaction with Thioglycolic acid. BODIPY was synthesized by the condensation reaction between aldehyde and pyrrole in dichloromethane, followed by in situ complexation with BF3·OEt2 in the presence of the base. Then it was functionalized with allyl bromide to achieve the double bond and thus be able to carry out the click reaction. The thiol−ene click was performed using DMPA (2,2-Dimethoxy-2-phenylacetophenone) as a photo-initiator in the presence of UV light (320–500 nm) in DMF at room temperature for 24 hours. Compounds were characterized by standard analytical techniques, including UV-Vis Spectroscopy, 1H, 13C, 19F NMR and mass spectroscopy. The results of this study will be important to link BODIPY to polymers through the thiol group offering a diversity of applications and functionalization. This new molecule can be tested as third-generation photosensitizers, in which the dye is targeted by antibodies or nanocarriers by cells, mainly in cancer cells, PDT and Photodynamic Antimicrobial Chemotherapy (PACT). According to our studies, it was possible to visualize a click reaction between allyl BODIPY and thioglycolic acid. Our team will also test the reaction with other thiol groups for comparison. Further, we will do the click reaction of BODIPY with a natural polymer linked with a thiol group. The results of the above compounds will be tested in PDT assays on various lung cancer cell lines.

Keywords: bodipy, click reaction, thioglycolic acid, allyl, thiol-ene click

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Authors: Yunjia Yang, Peng Li, Gordon Xu, Timothy Mahony, Bing Zhang, Neena Mitter, Karishma Mody

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Sheep flystrike is one of the most economically important diseases affecting the Australian sheep and wool industry (>356M/annually). Currently, control of Lucillia cuprina relies almost exclusively on chemicals controls, and the parasite has developed resistance to nearly all control chemicals used in the past. It is, therefore, critical to develop an alternative solution for the sustainable control and management of flystrike. RNA interference (RNAi) technologies have been successfully explored in multiple animal industries for developing parasites controls. This research project aims to develop a RNAi based biological control for sheep blowfly. Double-stranded RNA (dsRNA) has already proven successful against viruses, fungi, and insects. However, the environmental instability of dsRNA is a major bottleneck for successful RNAi. Bentonite polymer (BenPol) technology can overcome this problem, as it can be tuned for the controlled release of dsRNA in the gut challenging pH environment of the blowfly larvae, prolonging its exposure time to and uptake by target cells. To investigate the potential of BenPol technology for dsRNA delivery, four different BenPol carriers were tested for their dsRNA loading capabilities, and three of them were found to be capable of affording dsRNA stability under multiple temperatures (4°C, 22°C, 40°C, 55°C) in sheep serum. Based on stability results, dsRNA from potential targeted genes was loaded onto BenPol carriers and tested in larvae feeding assays, three genes resulting in knockdowns. Meanwhile, a primary blowfly embryo cell line (BFEC) derived from L. cuprina embryos was successfully established, aim for an effective insect cell model for testing RNAi efficacy for preliminary assessments and screening. The results of this study establish that the dsRNA is stable when loaded on BenPol particles, unlike naked dsRNA rapidly degraded in sheep serum. The stable nanoparticle delivery system offered by BenPol technology can protect and increase the inherent stability of dsRNA molecules at higher temperatures in a complex biological fluid like serum, providing promise for its future use in enhancing animal protection.

Keywords: lucilia cuprina, primary cell line establishment, RNA interference, insect cell transfection

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Authors: Sujatha Edla

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Introduction: New compounds and possible uses for the bioactive substances produced by freshwater cyanobacteria are constantly being discovered through research. Certain molecules are hazardous to the environment and human health, but others have potential applications in industry, biotechnology, and pharmaceuticals. These discoveries advance our knowledge of the varied functions these microbes perform in different ecosystems. Cyanobacterial silver nanoparticles (AgNPs) have special qualities and possible therapeutic advantages, which make them very promising for a range of medicinal uses. Aim: In our study; the attention was focused on the analysis and characterization of bioactive compounds extracted from freshwater cyanobacteria Planktothricoides raciorskii and its comparative study on Cyanobacteria-mediated silver nanoparticles synthesized by cell-free extract of Planktothricoides raciorskii. Material and Methods: A variety of bioactive secondary metabolites have been extracted, purified, and identified from cyanobacterial species using column chromatography, FTIR, and GC-MS/MS chromatography techniques and evaluated for antibacterial and cytotoxic studies, where the Cyanobacterial silver nanoparticles (CSNPs) were characterized by UV-Vis spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Fourier transform infrared (FTIR) analysis and were further tested for antibacterial and cytotoxic efficiency. Results: The synthesis of CSNPs was confirmed through visible color change and shift of peaks at 430–445 nm by UV-Vis spectroscopy. The size of CSNPs was between 22 and 34 nm and oval-shaped which were confirmed by SEM and TEM analyses. The FTIR spectra showed a new peak at the range of 3,400–3,460 cm−1 compared to the control, confirming the reduction of silver nitrate. The antibacterial activity of both crude bioactive compound extract and CSNPs showed remarkable activity with Zone of inhibition against E. coli with 9.5mm and 10.2mm, 13mm and 14.5mm against S. paratyphi, 9.2mm and 9.8mm zone of inhibition against K. pneumonia by both crude extract and CSNPs, respectively. The cytotoxicity as evaluated by extracts of Planktothricoides raciorskii against MCF7-Human Breast Adenocarcinoma cell line and HepG2- Human Hepatocellular Carcinoma cell line employing MTT assay gave IC50 value of 47.18ug/ml, 110.81ug/ml against MCF7cell line and HepG2 cell line, respectively. The cytotoxic evaluation of Planktothricoides raciorskii CSNPs against the MCF7cell line was 43.37 ug/ml and 20.88 ug/ml against the HepG2 cell line. Our ongoing research in this field aims to uncover the full therapeutic potential of cyanobacterial silver nanoparticles and address any associated challenges.

Keywords: cyanobacteria, silvernanoparticles, pharmaceuticals, bioactive compounds, cytotoxic

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Authors: Matthew E. Potter, Daniel J. Stewart, Lindsay M. Armstrong, Pier J. A. Sazio, Robert R. Raja

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Rising CO₂ levels in the atmosphere means that CO₂ is a highly desirable feedstock. This requires specific catalysts to be designed to activate this inert molecule, combining a catalytic site tailored for CO₂ transformations with a support that can readily adsorb CO₂. Metal organic frameworks (MOFs) are regularly used as CO₂ sorbents. The organic nature of the linker molecules, connecting the metal nodes, offers many post-synthesis modifications to introduce catalytic active sites into the frameworks. However, the metal nodes may be coordinatively unsaturated, allowing them to bind to organic moieties. Imidazoles have shown promise catalyzing the formation of cyclic carbonates from epoxides with CO₂. Typically, this synthesis route employs toxic reagents such as phosgene, liberating HCl. Therefore an alternative route with CO₂ is highly appealing. In this work we design active sites for CO₂ activation, by tethering substituted-imidazole organocatalytic species to the available Cr3+ metal nodes of a Cr-MIL-101 MOF, for the first time, to create a tailored species for carbon capture utilization applications. Our tailored design strategy combining a CO₂ sorbent, Cr-MIL-101, with an anchored imidazole results in a highly active and selective multifunctional catalyst, achieving turnover frequencies of over 750 hr-1. These findings demonstrate the synergy between the MOF framework and imidazoles for CO₂ utilization applications. Further, the effect of substrate variation has been explored yielding mechanistic insights into this process. Through characterization, we show that the structural and compositional integrity of the Cr-MIL-101 has been preserved on functionalizing the imidazoles. Further, we show the binding of the imidazoles to the Cr3+ metal nodes. This can be seen through our EPR study, where the distortion of the Cr3+ on binding to the imidazole shows the CO₂ binding site is close to the active imidazole. This has a synergistic effect, improving catalytic performance. We believe the combination of MOF support and organocatalyst allows many possibilities to generate new multifunctional catalysts for CO₂ utilisation. In conclusion, we have validated our design procedure, combining a known CO₂ sorbent, with an active imidazole species to create a unique tailored multifunctional catalyst for CO₂ utilization. This species achieves high activity and selectivity for the formation of cyclic carbonates and offers a sustainable alternative to traditional synthesis methods. This work represents a unique design strategy for CO₂ utilization while offering exciting possibilities for further work in characterization, computational modelling, and post-synthesis modification.

Keywords: carbonate, catalysis, MOF, utilisation

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Authors: Aloke Bapli, Debabrata Seth

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Graphene oxide (GO) is the two-dimensional (2D) nanoscale allotrope of carbon having several physiochemical properties such as high mechanical strength, high surface area, strong thermal and electrical conductivity makes it an important candidate in various modern applications such as drug delivery, supercapacitors, sensors etc. GO has been used in the photothermal treatment of cancers and Alzheimer’s disease etc. The main idea to choose GO in our work is that it is a surface active molecule, it has a large number of hydrophilic functional groups such as carboxylic acid, hydroxyl, epoxide on its surface and in basal plane. So it can easily interact with organic fluorophores through hydrogen bonding or any other kind of interaction and easily modulate the photophysics of the probe molecules. We have used different spectroscopic techniques for our work. The Ground-state absorption spectra and steady-state fluorescence emission spectra were measured by using UV-Vis spectrophotometer from Shimadzu (model-UV-2550) and spectrofluorometer from Horiba Jobin Yvon (model-Fluoromax 4P) respectively. All the fluorescence lifetime and anisotropy decays were collected by using time-correlated single photon counting (TCSPC) setup from Edinburgh instrument (model: LifeSpec-II, U.K.). Herein, we described the photophysics of a hydrophilic molecule 7-(n,n׀-diethylamino) coumarin-3-carboxylic acid (7-DCCA) in the reverse micelles containing GO. It was observed that photophysics of dye is modulated in the presence of GO compared to photophysics of dye in the absence of GO inside the reverse micelles. Here we have reported the solvent relaxation and rotational relaxation time in GO containing reverse micelle and compare our work with normal reverse micelle system by using 7-DCCA molecule. Normal reverse micelle means reverse micelle in the absence of GO. The absorption maxima of 7-DCCA were blue shifted and emission maxima were red shifted in GO containing reverse micelle compared to normal reverse micelle. The rotational relaxation time in GO containing reverse micelle is always faster compare to normal reverse micelle. Solvent relaxation time, at lower w₀ values, is always slower in GO containing reverse micelle compare to normal reverse micelle and at higher w₀ solvent relaxation time of GO containing reverse micelle becomes almost equal to normal reverse micelle. Here emission maximum of 7-DCCA exhibit bathochromic shift in GO containing reverse micelles compared to that in normal reverse micelles because in presence of GO the polarity of the system increases, as polarity increases the emission maxima was red shifted an average decay time of GO containing reverse micelle is less than that of the normal reverse micelle. In GO containing reverse micelle quantum yield, decay time, rotational relaxation time, solvent relaxation time at λₑₓ=375 nm is always higher than λₑₓ=405 nm, shows the excitation wavelength dependent photophysics of 7-DCCA in GO containing reverse micelles.

Keywords: photophysics, reverse micelle, rotational relaxation, solvent relaxation

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Authors: Bao-Fang Wen, Meng-Na Dai, Gao-Pei Zhu, Chen-Xi Zhang, Jing Sun, Xun-Bao Yin, Yu-Han Zhao, Hong-Wei Sun, Wei-Fen Zhang

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A drug-loaded nanoparticles containing berberine hydrochloride (BH/FA-CTS-NPs) was prepared. The physicochemical characterizations of BH/FA-CTS-NPs and the inhibitory effect on the HeLa cells were investigated. Folic acid-conjugated chitosan (FA-CTS) was prepared by amino reaction of folic acid active ester and chitosan molecules; BH/FA-CTS-NPs were prepared using ionic cross-linking technique with BH as a model drug. The morphology and particle size were determined by Transmission Electron Microscope (TEM). The average diameters and polydispersity index (PDI) were evaluated by Dynamic Light Scattering (DLS). The interaction between various components and the nanocomplex were characterized by Fourier Transform Infrared Spectroscopy (FT-IR). The entrapment efficiency (EE), drug-loading (DL) and in vitro release were studied by UV spectrophotometer. The effect of cell anti-migratory and anti-invasive actions of BH/FA-CTS-NPs were investigated using MTT assays, wound healing assays, Annexin-V-FITC single staining assays, and flow cytometry, respectively. HeLa nude mice subcutaneously transplanted tumor model was established and treated with different drugs to observe the effect of BH/FA-CTS-NPs in vivo on HeLa bearing tumor. The BH/FA-CTS-NPs prepared in this experiment have a regular shape, uniform particle size, and no aggregation phenomenon. The results of DLS showed that mean particle size, PDI and Zeta potential of BH/FA-CTS NPs were (249.2 ± 3.6) nm, 0.129 ± 0.09, 33.6 ± 2.09, respectively, and the average diameter and PDI were stable in 90 days. The results of FT-IR demonstrated that the characteristic peaks of FA-CTS and BH/FA-CTS-NPs confirmed that FA-CTS cross-linked successfully and BH was encapsulated in NPs. The EE and DL amount were (79.3 ± 3.12) % and (7.24 ± 1.41) %, respectively. The results of in vitro release study indicated that the cumulative release of BH/FA-CTS NPs was (89.48±2.81) % in phosphate-buffered saline (PBS, pH 7.4) within 48h; these results by MTT assays and wund healing assays indicated that BH/FA-CTS NPs not only inhibited the proliferation of HeLa cells in a concentration and time-dependent manner but can induce apoptosis as well. The subcutaneous xenograft tumor formation rate of human cervical cancer cell line HeLa in nude mice was 98% after inoculation for 2 weeks. Compared with BH group and BH/CTS-NPs group, the xenograft tumor growth of BH/FA-CTS-NPs group was obviously slower; the result indicated that BH/FA-CTS-NPs could significantly inhibit the growth of HeLa xenograft tumor. BH/FA-CTS NPs with the sustained release effect could be prepared successfully by the ionic crosslinking method. Considering these properties, block proliferation and impairing the migration of the HeLa cell line, BH/FA-CTS NPs could be an important compound for consideration in the treatment of cervical cancer.

Keywords: folic-acid, chitosan, berberine hydrochloride, nanoparticles, cervical cancer

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Authors: Jigar N. Shah, Hiral J. Shah, Praful D. Bharadia

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The major challenge faced by formulation scientists in transdermal drug delivery system is to overcome the inherent barriers related to skin permeation. The stratum corneum layer of the skin is working as the rate limiting step in transdermal transport and reduce drug permeation through skin. Many approaches have been used to enhance the penetration of drugs through this layer of the skin. The purpose of this study is to investigate the development and evaluation of a combined approach of drug carriers and iontophoresis as a vehicle to improve skin permeation of an analgesic drug. Iontophoresis is a non-invasive technique for transporting charged molecules into and through tissues by a mild electric field. It has been shown to effectively deliver a variety of drugs across the skin to the underlying tissue. In addition to the enhanced continuous transport, iontophoresis allows dose titration by adjusting the electric field, which makes personalized dosing feasible. Drug carrier could modify the physicochemical properties of the encapsulated molecule and offer a means to facilitate the percutaneous delivery of difficult-to-uptake substances. Recently, there are some reports about using liposomes, microemulsions and polymeric nanoparticles as vehicles for iontophoretic drug delivery. Niosomes, the nonionic surfactant-based vesicles that are essentially similar in properties to liposomes have been proposed as an alternative to liposomes. Niosomes are more stable and free from other shortcoming of liposomes. Recently, the transdermal delivery of certain drugs using niosomes has been envisaged and niosomes have proved to be superior transdermal nanocarriers. Proniosomes overcome some of the physical stability related problems of niosomes. The proniosomal structure was liquid crystalline-compact niosomes hybrid which could be converted into niosomes upon hydration. The combined use of drug carriers and iontophoresis could offer many additional benefits. The system was evaluated for Encapsulation Efficiency, vesicle size, zeta potential, Transmission Electron Microscopy (TEM), DSC, in-vitro release, ex-vivo permeation across skin and rate of hydration. The use of proniosomal gel as a vehicle for the transdermal iontophoretic delivery was evaluated in-vitro. The characteristics of the applied electric current, such as density, type, frequency, and on/off interval ratio were observed. The study confirms the synergistic effect of proniosomes and iontophoresis in improving the transdermal permeation profile of selected analgesic drug. It is concluded that proniosomal gel can be used as a vehicle for transdermal iontophoretic drug delivery under suitable electric conditions.

Keywords: iontophoresis, niosomes, permeation enhancement, transdermal delivery

Procedia PDF Downloads 357

Authors: Sulalit Bandyopadhyay, Muhammad Awais Ashfaq Alvi, Anuvansh Sharma, Wilhelm R. Glomm

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Release of drugs from nanogels and nanogel-based systems can occur under the influence of external stimuli like temperature, pH, magnetic fields and so on. pNIPAm-AAc nanogels respond to the combined action of both temperature and pH, the former being mostly determined by hydrophilic-to-hydrophobic transitions above the volume phase transition temperature (VPTT), while the latter is controlled by the degree of protonation of the carboxylic acid groups. These nanogels based systems are promising candidates in the field of drug delivery. Combining nanogels with magneto-plasmonic nanoparticles (NPs) introduce imaging and targeting modalities along with stimuli-response in one hybrid system, thereby incorporating multifunctionality. Fe@Au core-shell NPs possess optical signature in the visible spectrum owing to localized surface plasmon resonance (LSPR) of the Au shell, and superparamagnetic properties stemming from the Fe core. Although there exist several synthesis methods to control the size and physico-chemical properties of pNIPAm-AAc nanogels, yet, there is no comprehensive study that highlights the dependence of incorporation of one or more layers of NPs to these nanogels. In addition, effective determination of volume phase transition temperature (VPTT) of the nanogels is a challenge which complicates their uses in biological applications. Here, we have modified the swelling-collapse properties of pNIPAm-AAc nanogels, by combining with Fe@Au NPs using different solution based methods. The hydrophilic-hydrophobic transition of the nanogels above the VPTT has been confirmed to be reversible. Further, an analytical method has been developed to deduce the average VPTT which is found to be 37.3°C for the nanogels and 39.3°C for nanogel coated Fe@Au NPs. An opposite swelling –collapse behaviour is observed for the latter where the Fe@Au NPs act as bridge molecules pulling together the gelling units. Thereafter, Cyt C, a model protein drug and L-Dopa, a drug used in the clinical treatment of Parkinson’s disease were loaded separately into the nanogels and nanogel coated Fe@Au NPs, using a modified breathing-in mechanism. This gave high loading and encapsulation efficiencies (L Dopa: ~9% and 70µg/mg of nanogels, Cyt C: ~30% and 10µg/mg of nanogels respectively for both the drugs. The release kinetics of L-Dopa, monitored using UV-vis spectrophotometry was observed to be rather slow (over several hours) with highest release happening under a combination of high temperature (above VPTT) and acidic conditions. However, the release of L-Dopa from nanogel coated Fe@Au NPs was the fastest, accounting for release of almost 87% of the initially loaded drug in ~30 hours. The chemical structure of the drug, drug incorporation method, location of the drug and presence of Fe@Au NPs largely alter the drug release mechanism and the kinetics of these nanogels and Fe@Au NPs coated with nanogels.

Keywords: controlled release, nanogels, volume phase transition temperature, l-dopa

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Authors: Kanti Sapkota, Do Hyun Lee, Sung Soo Han

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Nanocomposites have been widely used in various fields such as electronics, catalysis, and in chemical, biological, biomedical and optical fields. They display broad biomedical properties like antidiabetic, anticancer, antioxidant, antimicrobial and antibacterial activities. Moreover, nanomaterials have been used for wastewater treatment. Particularly, bimetallic hybrid nanocomposites exhibit unique features as compared to their monometallic components. Hybrid nanomaterials not only afford the multifunctionality endowed by their constituents but can also show synergistic properties. In addition, these hybrid nanomaterials have noteworthy catalytic and optical properties. Notably, Au−Ag based nanoparticles can be employed in sensor and catalysis due to their characteristic composition-tunable plasmonic properties. Due to their importance and usefulness, various efforts were developed for their preparation. Generally, chemical methods have been described to synthesize such bimetallic nanocomposites. In such chemical synthesis, harmful and hazardous chemicals cause environmental contamination and increase toxicity levels. Therefore, ecologically benevolent processes for the synthesis of nanomaterials are highly desirable to diminish such environmental and safety concerns. In this regard, here we disclose a simple, cost-effective, external additive free and eco-friendly method for the synthesis of Au-Ag@AgCl nanocomposites using Nephrolepis cordifolia root extract. Au-Ag@AgCl NCs were obtained by the simultaneous reduction of cationic Ag and Au into AgCl in the presence of plant extract. The particle size of 10 to 50 nm was observed with the average diameter of 30 nm. The synthesized nanocomposite was characterized by various modern characterization techniques. For example, UV−visible spectroscopy was used to determine the optical activity of the synthesized NCs, and Fourier transform infrared (FT-IR) spectroscopy was employed to investigate the functional groups present in the biomolecules that were responsible for both reducing and capping agents during the formation of nanocomposites. Similarly, powder X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA) and energy-dispersive X-ray (EDX) spectroscopy were used to determine crystallinity, size, oxidation states, thermal stability and weight loss of the synthesized nanocomposites. As a synthetic application, the synthesized nanocomposite exhibited excellent catalytic activity for the multicomponent synthesis of biologically interesting quinoline molecules via domino annulation-aromatization reaction of aniline, arylaldehyde, and phenyl acetylene derivatives. Interestingly, the nanocatalyst was efficiently recycled for five times without substantial loss of catalytic properties.

Keywords: nanoparticles, catalysis, multicomponent, quinoline

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Authors: Peter. M. Kusen, Georg Wandrey, Christopher Probst, Dietrich Kohlheyer, Jochen Buchs, Jorg Pietruszkau

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Light as a stimulus provides the capability to develop regulation techniques for customizable gene expression. A great advantage is the extremely flexible and accurate dosing that can be performed in a non invasive and sterile manner even for high throughput technologies. Therefore, light regulation in a multiwell microbioreactor system was realized providing the opportunity to control gene expression with outstanding complexity. A light-regulated gene expression system in Saccharomyces cerevisiae was designed applying the strategy of caged compounds. These compounds are photo-labile protected and therefore biologically inactive regulator molecules which can be reactivated by irradiation with certain light conditions. The “caging” of a repressor molecule which is consumed after deprotection was essential to create a flexible expression system. Thereby, gene expression could be temporally repressed by irradiation and subsequent release of the active repressor molecule. Afterwards, the repressor molecule is consumed by the yeast cells leading to reactivation of gene expression. A yeast strain harboring a construct with the corresponding repressible promoter in combination with a fluorescent marker protein was applied in a Photo-BioLector platform which allows individual irradiation as well as online fluorescence and growth detection. This device was used to precisely control the repression duration by adjusting the amount of released repressor via different irradiation times. With the presented screening platform the regulation of complex expression procedures was achieved by combination of several repression/derepression intervals. In particular, a stepwise increase of temporally-constant expression levels was demonstrated which could be used to study concentration dependent effects on cell functions. Also linear expression rates with variable slopes could be shown representing a possible solution for challenging protein productions, whereby excessive production rates lead to misfolding or intoxication. Finally, the very flexible regulation enabled accurate control over the expression induction, although we used a repressible promoter. Summing up, the continuous online regulation of gene expression has the potential to synchronize gene expression levels to optimize metabolic flux, artificial enzyme cascades, growth rates for co cultivations and many other applications addicted to complex expression regulation. The developed light-regulated expression platform represents an innovative screening approach to find optimization potential for production processes.

Keywords: caged-compounds, gene expression regulation, optogenetics, photo-labile protecting group

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Authors: Rima Alfaraj, Abeer Alarawi, Murtadha AlTammar

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The global energy landscape heavily relies on the oil and gas industry, which faces the critical challenge of reducing its carbon footprint. To address this issue, the integration of advanced materials like aerogels has emerged as a promising solution to enhance sustainability and environmental performance within the industry. This study thoroughly examines the application of aerogel-based technologies in the oil and gas sector, focusing particularly on their role in carbon capture and storage (CCS) initiatives. Aerogels, known for their exceptional properties, such as high surface area, low density, and customizable pore structure, have garnered attention for their potential in various CCS strategies. The review delves into various fabrication techniques utilized in producing aerogel materials, including sol-gel, supercritical drying, and freeze-drying methods, to assess their suitability for specific industry applications. Beyond fabrication, the practicality of aerogel materials in critical areas such as flow assurance, enhanced oil recovery, and thermal insulation is explored. The analysis spans a wide range of applications, from potential use in pipelines and equipment to subsea installations, offering valuable insights into the real-world implementation of aerogels in the oil and gas sector. The paper also investigates the adsorption and storage capabilities of aerogel-based sorbents, showcasing their effectiveness in capturing and storing carbon dioxide (CO₂) molecules. Optimization of pore size distribution and surface chemistry is examined to enhance the affinity and selectivity of aerogels towards CO₂, thereby improving the efficiency and capacity of CCS systems. Additionally, the study explores the potential of aerogel-based membranes for separating and purifying CO₂ from oil and gas streams, emphasizing their role in the carbon capture and utilization (CCU) value chain in the industry. Emerging trends and future perspectives in integrating aerogel-based technologies within the oil and gas sector are also discussed, including the development of hybrid aerogel composites and advanced functional components to further enhance material performance and versatility. By synthesizing the latest advancements and future directions in aerogel used for CCS applications in the oil and gas industry, this review offers a comprehensive understanding of how these innovative materials can aid in transitioning towards a more sustainable and environmentally conscious energy landscape. The insights provided can assist in strategic decision-making, drive technology development, and foster collaborations among academia, industry, and policymakers to promote the widespread adoption of aerogel-based solutions in the oil and gas sector.

Keywords: CCS, porous, carbon capture, oil and gas, sustainability

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Authors: Michalina Aniola, Andrzej Katrusiak

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4,4-Bipyridine is an important compound often used in chemical practice and more recently frequently applied for designing new metal organic framework (MoFs). Here we present a systematic high-pressure study of its hydrobromide salt. 4,4-Bipyridine hydrobromide monohydrate, 44biPyHBrH₂O, at ambient-pressure is orthorhombic, space group P212121 (phase a). Its hydrostatic compression shows that it is stable to 1.32 GPa at least. However, the recrystallization above 0.55 GPa reveals a new hidden b-phase (monoclinic, P21/c). Moreover, when the 44biPyHBrH2O is heated to high temperature the chemical reactions of this compound in methanol solution can be observed. High-pressure experiments were performed using a Merrill-Bassett diamond-anvil cell (DAC), modified by mounting the anvils directly on the steel supports, and X-ray diffraction measurements were carried out on a KUMA and Excalibur diffractometer equipped with an EOS CCD detector. At elevated pressure, the crystal of 44biPyHBrH₂O exhibits several striking and unexpected features. No signs of instability of phase a were detected to 1.32 GPa, while phase b becomes stable at above 0.55 GPa, as evidenced by its recrystallizations. Phases a and b of 44biPyHBrH2O are partly isostructural: their unit-cell dimensions and the arrangement of ions and water molecules are similar. In phase b the HOH-Br- chains double the frequency of their zigzag motifs, compared to phase a, and the 44biPyH+ cations change their conformation. Like in all monosalts of 44biPy determined so far, in phase a the pyridine rings are twisted by about 30 degrees about bond C4-C4 and in phase b they assume energy-unfavorable planar conformation. Another unusual feature of 44biPyHBrH2O is that all unit-cell parameters become longer on the transition from phase a to phase b. Thus the volume drop on the transition to high-pressure phase b totally depends on the shear strain of the lattice. Higher temperature triggers chemical reactions of 44biPyHBrH2O with methanol. When the saturated methanol solution compound precipitated at 0.1 GPa and temperature of 423 K was required to dissolve all the sample, the subsequent slow recrystallization at isochoric conditions resulted in disalt 4,4-bipyridinium dibromide. For the 44biPyHBrH2O sample sealed in the DAC at 0.35 GPa, then dissolved at isochoric conditions at 473 K and recrystallized by slow controlled cooling, a reaction of N,N-dimethylation took place. It is characteristic that in both high-pressure reactions of 44biPyHBrH₂O the unsolvated disalt products were formed and that free base 44biPy and H₂O remained in the solution. The observed reactions indicate that high pressure destabilized ambient-pressure salts and favors new products. Further studies on pressure-induced reactions are carried out in order to better understand the structural preferences induced by pressure.

Keywords: conformation, high-pressure, negative area compressibility, polymorphism

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Authors: Caroline Mendes, Mary McNamara, Orla Howe

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For chemotherapy, a drug delivery system should be able to specifically target cancer cells and deliver the therapeutic dose without affecting normal cells. Folate receptors (FR) can be considered key targets since they are commonly over-expressed in cancer cells and they are the molecular marker used in this study. Here, cyclodextrin (CD) has being studied as a vehicle for delivering the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within the CD cavity. In this study, β-CD has been modified using folic acid so as to specifically target the FR molecular marker. Thus, the system studied here for drug delivery consists of β-CD, folic acid and MTX (CDEnFA:MTX). Cellular uptake of folic acid is mediated with high affinity by folate receptors while the cellular uptake of antifolates, such as MTX, is mediated with high affinity by the reduced folate carriers (RFCs). This study addresses the gene (mRNA) and protein expression levels of FRs and RFCs in the cancer cell lines CaCo-2, SKOV-3, HeLa, MCF-7, A549 and the normal cell line BEAS-2B, quantified by real-time polymerase chain reaction (real-time PCR) and flow cytometry, respectively. From that, four cell lines with different levels of FRs, were chosen for cytotoxicity assays of MTX and CDEnFA:MTX using the MTT assay. Real-time PCR and flow cytometry data demonstrated that all cell lines ubiquitously express moderate levels of RFC. These experiments have also shown that levels of FR protein in CaCo-2 cells are high, while levels in SKOV-3, HeLa and MCF-7 cells are moderate. A549 and BEAS-2B cells express low levels of FR protein. FRs are highly expressed in all the cancer cell lines analysed when compared to the normal cell line BEAS-2B. The cell lines CaCo-2, MCF-7, A549 and BEAS-2B were used in the cell viability assays. 48 hours treatment with the free drug and the complex resulted in IC50 values of 93.9 µM ± 9.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 10.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 8.5 for A549 and 132.6 µM ± 12.1 and 288.1 µM ± 16.3 for BEAS-2B. These results demonstrate that MTX is more toxic towards cell lines expressing low levels of FR, such as the BEAS-2B. More importantly, these results demonstrate that the inclusion complex CDEnFA:MTX showed greater cytotoxicity than the free drug towards the high FR expressing CaCo-2 cells, indicating that it has potential to target this receptor, enhancing the specificity and the efficiency of the drug.

Keywords: cyclodextrins, cancer treatment, drug delivery, folate receptors, reduced folate carriers

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Authors: Nicola G. G. Cecca

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In Italian IPSSEOAs, high schools that give a vocational education to students that will work in the field of Enogastronomy and Hotel Management, the course of Food Science allows the students to start and see food as a mixture of substances that they will transform during their profession. These substances are characterized not only by a chemical composition but also by a molecular structure that makes them nutritionally active. But the increasing number of new products proposed by Food Industry, the modern techniques of production and transformation, the innovative preparations required by customers have made many information reported in the most wide spread Food Science textbooks not up-to-date or too poor for the people who will work in catering sector. Often Authors offer information aged to Bohr’s Atomic Model and to the ‘Octet Rule’ proposed by G.N. Lewis to describe the Chemical Bond, without giving any reference to new as Orbital Atomic Model and Molecular Orbital Theory that, in the meantime, start to be old themselves. Furthermore, this antiquated information precludes an easy understanding of a wide range of properties of nutritive substances and many reactions in which the food constituents are involved. In this paper, our attention is pointed out to use GEOMAG™ to represent the dynamics with which the chemical bond is formed during the synthesis of the molecules. GEOMAG™ is a toy, produced by the Swiss Company Geomagword S.A., pointed to stimulate in children, aged between 6-10 years, their fantasy and their handling ability and constituted by metallic spheres and metallic magnetic bars coated by coloured plastic materials. The simulation carried out with GEOMAG™ is based on the similitude existing between the Coulomb’s force and the magnetic attraction’s force and in particular between the formulae with which they are calculated. The electrostatic force (F in Newton) that allows the formation of the chemical bond can be calculated by mean Fc = kc q1 q2/d2 where: q1 e q2 are the charge of particles [in Coulomb], d is the distance between the particles [in meters] and kc is the Coulomb’s constant. It is surprising to observe that the attraction’s force (Fm) acting between the magnetic extremities of GEOMAG™ used to simulate the chemical bond can be calculated in the same way by using the formula Fm = km m1 m2/d2 where: m1 e m2 represent the strength of the poles [A•m], d is the distance between the particles [m], km = μ/4π in which μ is the magnetic permeability of medium [N•A-2]. The magnetic attraction can be tested by students by trying to keep the magnetic elements of GEOMAG™ separate by hands or trying to measure by mean an appropriate dynamometric system. Furthermore, by using a dynamometric system to measure the magnetic attraction between the GEOMAG™ elements is possible draw a graphic F=f(d) to verify that the curve obtained during the simulation is very similar to that one hypnotized, around the 1920’s by Linus Pauling to describe the formation of H2+ in according with Molecular Orbital Theory.

Keywords: chemical bond, molecular orbital theory, magnetic attraction force, GEOMAG™

Procedia PDF Downloads 241

Authors: Safaa S. Hassan, Mohammed H. Elbakry, Safwat A. Mangoura, Zainab M. Omar

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Background: Liver fibrosis is the main reason for increased mortality in chronic liver disease. It has no standard treatment. Antioxidants from a variety of sources are capable of slowing or preventing oxidation of other molecules. Aim: to evaluate the hepatoprotective effect of vit. C, vit. E and gallic acid in comparison to silymarin in the rat model of carbon tetrachloride induced liver fibrosis and their possible mechanisms of action. Material& Methods: A total number of 60 adult male albino rats 160-200gm were divided into six equal groups; received subcutaneous (s.c) injection for 8 weeks. Group I: as control. Group II: received 1.5 mL/kg of CCL4 .Group III: CCL4 and co- treatment with silymarin 100mg/kg p.o. daily. Group IV: CCL4 and co-treatment with vit. C 50mg/kg p.o. daily. Group V: CCL4 and co-treatment with vit. E 200mg/kg. p.o. Group VI: CCL4 and co-treatment with Gallic acid 100mg/kg. p.o. daily. Liver was processed for histological and immunohistochemical examination. Levels of AST, ALT, ALP, reduced GSH, MDA, SOD and hydroxyproline concentration were measured and evaluated statistically. Results: Light and electron microscopic examination of liver of group II exhibited foci of altered cells with dense nuclei and vacuolated, granular cytoplasm, mononuclear cell infiltration in portal areas, profuse collagen fiber deposits were found around portal tract, more intense staining α-SMA-positive cells occupied most of the liver fibrosis tissue, electron lucent areas in the cytoplasm of the hepatocytes, margination of nuclear chromatin. Treatment by any of the antioxidants variably reduced the hepatic structural changes induced by CCL4. Biochemical analysis showed that carbon tetrachloride significantly increased the levels of serum AST, ALT, ALP, hepatic malondialdehyde and hydroxyproline content. Moreover, it decreased the activities of superoxide dismutase and glutathione. Treatment with silymarin, gallic acid, vit. C and vit. E decreased significantly the AST, ALT, and ALP levels in plasma, MDA and hydroxyproline and increased the activities of SOD and glutathione in liver tissue. The effect of administration of CCl4 was improved with the used antioxidants in variable degrees. The most efficient antioxidant was silymarin followed by gallic acid and vit. C then vit. E. It is possibly due to their antioxidant effect, free radical scavenging properties and the reduction of oxidant dependent activation and proliferation of HSCs. Conclusion: So these antioxidants can be a promising drugs candidate for ameliorating liver fibrosis better than the use of the drugs and their side effects.

Keywords: antioxidant, ccl4, gallic acid, liver fibrosis

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Authors: A. Hamza, H. Kathyayini, N. Nagaraju

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Aluminophosphates, both amorphous and crystalline materials find applications as adsorbents, ceramics, and pigments and as catalysts/catalyst supports in organic fine chemical synthesis. Most of the applications are varied depending on the type of metal incorporated, particle size, surface area, porosity and morphology of aluminophosphate. The porous and surface properties of these materials are normally fine-tuned by adopting various preparation methodologies. Numerous crystalline microporous and mesoporous aluminophosphates and metal-aluminophosphates have been reported in literature, in which the synthesis has been carried out by using structure directing organic molecules/surfactants. In present work, amorphous aluminophosphate (AlP) and metal-aluminophosphates MAlP (M = Cu, Zn, Cr, Fe, Ce and Zr) and their mixed forms M-1M2AlP are prepared under a typical precipitation condition, i.e. at low temperature in order to keep the Von-Weirmann relative super saturation of the precipitating medium and obtain small size precipitate particles. These materials are prepared without using any surfactants. All materials are thoroughly characterised for surface and bulk properties by N2 adsorption-desorption technique, XRD, FT-IR, TG and SEM. The materials are also analysed for the amount and the strength of their surface acid sites, by NH3-TPD and CO2-TPD techniques respectively. All the materials prepared in the work are investigated for their catalytic activity in following applications in the synthesis of industrially important Jasminaldehyde via, aldol condensation of n-heptanal and benzaldehyde, in the synthesis of biologically important chalcones by Claisen-shmidth condensation of benzaldehyde and substituted chalcones. The effect of the amount of the catalysts, duration of the reaction, temperature of the reaction, molar ratio of the reactants has been studied. The porosity of pure aluminophosphate is found to be changed significantly by the incorporation of transition metals during preparation of aluminophosphate. The pore size increased from microporous to mesoporous and finally to macroporous by following order of metals Cu = Zn < Cr < Ce < Fe = Zr. The change in surface area and porosity of double metal-aluminophosphates depended on the concentration of both the metals. The acidity of aluminophosphate is either increased or decreased which depended on the type and valence of metals loaded. A good number of basic sites are created in metal-aluminophosphates irrespective of the metals used. A maximum catalytic activity for synthesis of both jasminaldehyde and chalcone is obtained by FeAlP as catalysts; these materials are characterized by decreased strength and concentration of acidic sites with optimum level basic sites.

Keywords: amorphous metal-aluminophosphates, surface properties, acidic-basic properties, Aldol, Claisen-Shmidth condensation, jasminaldehyde, chalcone

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Authors: A. Kesraoui, M. Seffen

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Applications of adsorption onto activated carbon for water treatment are well known. The process has been demonstrated to be widely effective for removing dissolved organic substances from wastewaters, but this treatment has a major drawback is the high operating cost. The main goal of our research work is to improve the retention capacity of Tunisian biomass for the depollution of industrial wastewater and retention of pollutants considered toxic. The biosorption process is based on the retention of molecules and ions onto a solid surface composed of biological materials. The evaluation of the potential use of these materials is important to propose as an alternative to the adsorption process generally expensive, used to remove organic compounds. Indeed, these materials are very abundant in nature and are low cost. Certainly, the biosorption process is effective to remove the pollutants, but it presents a slow kinetics. The improvement of the biosorption rates is a challenge to make this process competitive with respect to oxidation and adsorption onto lignocellulosic fibers. In this context, the alternating current appears as a new alternative, original and a very interesting phenomenon in the acceleration of chemical reactions. Our main goal is to increase the retention acceleration of dyes (indigo carmine, methylene blue) and phenol by using a new alternative: alternating current. The adsorption experiments have been performed in a batch reactor by adding some of the adsorbents in 150 mL of pollutants solution with the desired concentration and pH. The electrical part of the mounting comprises a current source which delivers an alternating current voltage of 2 to 15 V. It is connected to a voltmeter that allows us to read the voltage. In a 150 mL capacity cell, we plunged two zinc electrodes and the distance between two Zinc electrodes has been 4 cm. Thanks to alternating current, we have succeeded to improve the performance of activated carbon by increasing the speed of the indigo carmine adsorption process and reducing the treatment time. On the other hand, we have studied the influence of the alternating current on the biosorption rate of methylene blue onto Luffa cylindrica fibers and the hybrid material (Luffa cylindrica-ZnO). The results showed that the alternating current accelerated the biosorption rate of methylene blue onto the Luffa cylindrica and the Luffa cylindrica-ZnO hybrid material and increased the adsorbed amount of methylene blue on both adsorbents. In order to improve the removal of phenol, we performed the coupling between the alternating current and the biosorption onto two adsorbents: Luffa cylindrica and the hybrid material (Luffa cylindrica-ZnO). In fact, the alternating current has succeeded to improve the performance of adsorbents by increasing the speed of the adsorption process and the adsorption capacity and reduce the processing time.

Keywords: adsorption, alternating current, dyes, modeling

Procedia PDF Downloads 136

Authors: Ayla Roberta Galaco, Juliana Fonseca De Lima, Osvaldo Antonio Serra

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Coordination polymers, also known as metal-organic frameworks (MOFs) or lanthanoide organic frameworks (LOFs) have been reported due of their promising applications in gas storage, separation, catalysis, luminescence, magnetism, drug delivery, and so on. As a type of organic–inorganic hybrid materials, the properties of coordination polymers could be chosen by deliberately selecting the organic and inorganic components. LOFs have received considerable attention because of their properties such as porosity, luminescence, and magnetism. Methods such as solvothermal synthesis are important as a strategy to control the structural and morphological properties as well as the composition of the target compounds. In this work the first solvothermal synthesis was employed to obtain the compound [Y0.4,Yb0.4,Er0.2(dmf)(for)(H2O)(tft)], by using terephthalic acid (tft) and oxalic acid, decomposed in formate (for), as ligands; Yttrium, Ytterbium and, Erbium as metal centers, in DMF and water for 4 days under 160 °C. The semi-rigid terephthalic acid (dicarboxylic) coordinates with Ln3+ ions and also is possible to form a polyfunctional bridge. On the other hand, oxalate anion has no high-energy vibrational groups, which benefits the excitation of Yb3+ in upconversion process. It was observed that the compounds with water molecules in the coordination sphere of the lanthanoide ions cause lower crystalline properties and change the structure of the LOF (1D, 2D, 3D). In the FTIR, the bands at 1589 and 1500 cm-1 correspond to the asymmetric stretching vibration of –COO. The band at 1383 cm-1 is assigned to the symmetric stretching vibration of –COO. Single crystal X-ray diffraction study reveals an infinite 3D coordination framework that crystalizes in space group P21/c. The other three products, [TR(chel)(ofd)0,5(H2O)2], where TR= Eu3+, Y3, and Yb3+/Er3+ were obtained by using 1, 2-phenylenedioxydiacetic acid (ofd) and chelidonic acid (chel) as organic ligands. Thermal analysis shows that the lanthanoide organic frameworks do not collapse at temperatures below 250 °C. By the polycrystalline X-ray diffraction patterns (PXRD) it was observed that the compounds with Eu3+, Y3+, and Yb3+/Er3+ ions are isostructural. From PXRD patterns, high crystallinity can be noticed for the complexes. The final products were characterized by single X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), energy dispersive spectroscopy (EDS) and thermogravimetric analysis (TGA). The X-ray diffraction (XRD) is an effective method to investigate crystalline properties of synthesized materials. The solid crystal obtained in the synthesis show peaks at 2θ < 10°, indicating the MOF formation. The chemical composition of LOFs was also confirmed by EDS.

Keywords: isostructural, lanthanoids, lanthanoids organic frameworks (LOFs), metal organic frameworks (MOFs), thermogravimetry, X-Ray diffraction

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Authors: Abdolamir Allameh, Shahnaz Esmaeili, Mina Allameh, Safoura Khajeniazi

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Stem cells with therapeutic applications can be isolated from human placenta/umblical cord blood (UCB) as well as the cord tissue (UC). Stem cells in culture are vulnerable to oxidative stress, particularly when subjected to differentiation process. The aim of this study was to examine the chnages in the rate of oxidation that occurs to cellular macromolecules during hepatic differentiation of mononuclear cells (MSCs). In addition, the impact of the hepatic differentiation process of MSC on cellular and biological activity of the cells will be undertaken. For this purpose, first mononuclear cells (MNCs) were isolated from human UCB which was obtained from a healthy full-term infant. The cells were cultured at a density of 3×10⁵ cells/cm² in DMEM- low-glucose culture media supplemented with 20% FBS, 2 mM L-glutamine, 100 μg/ml streptomycin and 100 U/ml penicillin. Cell cultures were then incubated at 37°C in a humidified 5% CO₂ incubator. After removing non-adherent cells by replacing culture medium, fibroblast-like adherent cells were resuspended in 0.25% trypsin-EDTA and plated in 25 cm² flasks (1×10⁴/ml). Characterization of the MSCs was routinely done by observing their morphology and growth curve. MSCs were subjected to a 2-step hepatocyte differentiation protocol in presence of hepatocyte growth factor (HGF), dexamethazone (DEX) and oncostatin M (OSM). The hepatocyte-like cells derived from MSCs were checked every week for 3 weeks for changes in lipid peroxidation, protein carbonyl formation and DNA oxidation i.e., 8-hydroxy-2'-deoxyguanosine (8-OH-dG) assay. During the 3-week differentiation process of MSCs to hepatocyte-like cells we found that expression liver-specific markers such as albumin, was associated with increased levels of lipid peroxidation and protein carbonyl formation. Whereas, undifferentiated MSCs has relatively low levels of lipid peroxidation products. There was a significant increase ( p < 0.05) in lipid peroxidation products in hepatocytes on days 7, 14, and 21 of differentiation. Likewise, the level of protein carbonyls in the cells was elevated during the differentiation. The level of protein carbonyls measured in hepatocyte-like cells obtained 3 weeks after differentiation induction was estimated to be ~6 fold higher compared to cells recovered on day 7 of differentiation. On the contrary, there was a small but significant decrease in DNA damage marker (8-OH-dG) in hepatocytes recovered 3 weeks after differentiation onset. The level of 8-OHdG which was in consistent with formation of reactive oxygen species (ROS). In conclusion, this data suggest that despite the elevation in oxidation of lipid and protein molecules during hepatocyte development, the cells were normal in terms of DNA integrity, morphology, and biologically activity.

Keywords: adult stem cells, DNA integrity, free radicals, hepatic differentiation

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Authors: Zoltan Sebestyen, Eszter Barta-Rajnai, Emma Jakab, Zsuzsanna Czegeny

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Extraction of the energy content of lignocellulosic biomass is one of the possible pathways to reduce the greenhouse gas emission derived from the burning of the fossil fuels. The application of the bioenergy can mitigate the energy dependency of a country from the foreign natural gas and the petroleum. The diversity of the plant materials makes difficult the utilization of the raw biomass in power plants. This problem can be overcome by the application of thermochemical techniques. Pyrolysis is the thermal decomposition of the raw materials under inert atmosphere at high temperatures, which produces pyrolysis gas, biooil and charcoal. The energy content of these products can be exploited by further utilization. The differences in the chemical and physical properties of the raw biomass materials can be reduced by the use of torrefaction. Torrefaction is a promising mild thermal pretreatment method performed at temperatures between 200 and 300 °C in an inert atmosphere. The goal of the pretreatment from a chemical point of view is the removal of water and the acidic groups of hemicelluloses or the whole hemicellulose fraction with minor degradation of cellulose and lignin in the biomass. Thus, the stability of biomass against biodegradation increases, while its energy density increases. The volume of the raw materials decreases so the expenses of the transportation and the storage are reduced as well. Biooil is the major product during pyrolysis and an important by-product during torrefaction of biomass. The composition of biooil mostly depends on the quality of the raw materials and the applied temperature. In this work, thermoanalytical techniques have been used to study the qualitative and quantitative composition of the pyrolysis and torrefaction oils of a woody (black locust) and two herbaceous samples (rape straw and wheat straw). The biooil contains C5 and C6 anhydrosugar molecules, as well as aromatic compounds originating from hemicellulose, cellulose, and lignin, respectively. In this study, special emphasis was placed on the formation of the lignin monomeric products. The structure of the lignin fraction is different in the wood and in the herbaceous plants. According to the thermoanalytical studies the decomposition of lignin starts above 200 °C and ends at about 500 °C. The lignin monomers are present among the components of the torrefaction oil even at relatively low temperatures. We established that the concentration and the composition of the lignin products vary significantly with the applied temperature indicating that different decomposition mechanisms dominate at low and high temperatures. The evolutions of decomposition products as well as the thermal stability of the samples were measured by thermogravimetry/mass spectrometry (TG/MS). The differences in the structure of the lignin products of woody and herbaceous samples were characterized by the method of pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS). As a statistical method, principal component analysis (PCA) has been used to find correlation between the composition of lignin products of the biooil and the applied temperatures.

Keywords: pyrolysis, torrefaction, biooil, lignin

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Authors: Yogita Patil-Sen

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Superparamagnetic Iron Oxide Nanoparticles (SPIONs) have become increasingly important materials for separation of specific bio-molecules, drug delivery vehicle, contrast agent for MRI and magnetic hyperthermia for cancer therapy. Hyperthermia is emerging as an alternative cancer treatment to the conventional radio- and chemo-therapy, which have harmful side effects. When subjected to an alternating magnetic field, the magnetic energy of SPIONs is converted into thermal energy due to movement of particles. The ability of SPIONs to generate heat and potentially kill cancerous cells, which are more susceptible than the normal cells to temperatures higher than 41 °C forms the basis of hyerpthermia treatement. The amount of heat generated depends upon the magnetic properties of SPIONs which in turn is affected by their properties such as size and shape. One of the main problems associated with SPIONs is particle aggregation which limits their employability in in vivo drug delivery applications and hyperthermia cancer treatments. Coating the iron oxide core with thermally responsive lipid based nanostructures tend to overcome the issue of aggregation as well as improve biocompatibility and can enhance drug loading efficiency. Herein we report suitability of SPIONs and silica coated core-shell SPIONs, which are further, coated with various lipids for drug delivery and magnetic hyperthermia applications. The synthesis of nanoparticles is carried out using the established methods reported in the literature with some modifications. The nanoparticles are characterised using Infrared spectroscopy (IR), X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM) and Vibrating Sample Magnetometer (VSM). The heating ability of nanoparticles is tested under alternating magnetic field. The efficacy of the nanoparticles as drug carrier is also investigated. The loading of an anticancer drug, Doxorubicin at 18 °C is measured up to 48 hours using UV-visible spectrophotometer. The drug release profile is obtained under thermal incubation condition at 37 °C and compared with that under the influence of alternating magnetic field. The results suggest that the nanoparticles exhibit superparamagnetic behaviour, although coating reduces the magnetic properties of the particles. Both the uncoated and coated particles show good heating ability, again it is observed that coating decreases the heating behaviour of the particles. However, coated particles show higher drug loading efficiency than the uncoated particles and the drug release is much more controlled under the alternating magnetic field. Thus, the results demonstrate that lipid coated SPIONs exhibit potential as drug delivery vehicles for magnetic hyperthermia based cancer therapy.

Keywords: drug delivery, hyperthermia, lipids, superparamagnetic iron oxide nanoparticles (SPIONS)

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Authors: Soma Banerjee, Aamen Talukdar, Argha Mandal, Dipankar Chaudhuri

Abstract:

Japanese Encephalitis is a major infectious disease with nearly half the world’s population living in areas where it is prevalent. Currently, treatment for it involves only supportive care and symptom management through vaccination. Due to the lack of antiviral drugs against Japanese Encephalitis Virus (JEV), the quest for such agents remains a priority. For these reasons, simulation studies of drug targets against JEV are important. Towards this purpose, docking experiments of the kinase inhibitors were done against the chosen target NS3 helicase as it is a nucleoside binding protein. Previous efforts regarding computational drug design against JEV revealed some lead molecules by virtual screening using public domain software. To be more specific and accurate regarding finding leads, in this study a proprietary software Schrödinger-GLIDE has been used. Druggability of the pockets in the NS3 helicase crystal structure was first calculated by SITEMAP. Then the sites were screened according to compatibility with ATP. The site which is most compatible with ATP was selected as target. Virtual screening was performed by acquiring ligands from databases: KinaseSARfari, KinaseKnowledgebase and Published inhibitor Set using GLIDE. The 25 ligands with best docking scores from each database were re-docked in XP mode. Protein structure alignment of NS3 was performed using VAST against MMDB, and similar human proteins were docked to all the best scoring ligands. The low scoring ligands were chosen for further studies and the high scoring ligands were screened. Seventy-three ligands were listed as the best scoring ones after performing HTVS. Protein structure alignment of NS3 revealed 3 human proteins with RMSD values lesser than 2Å. Docking results with these three proteins revealed the inhibitors that can interfere and inhibit human proteins. Those inhibitors were screened. Among the ones left, those with docking scores worse than a threshold value were also removed to get the final hits. Analysis of the docked complexes through 2D interaction diagrams revealed the amino acid residues that are essential for ligand binding within the active site. Interaction analysis will help to find a strongly interacting scaffold among the hits. This experiment yielded 21 hits with the best docking scores which could be investigated further for their drug like properties. Aside from getting suitable leads, specific NS3 helicase-inhibitor interactions were identified. Selection of Target modification strategies complementing docking methodologies which can result in choosing better lead compounds are in progress. Those enhanced leads can lead to better in vitro testing.

Keywords: antivirals, docking, glide, high-throughput virtual screening, Japanese encephalitis, ns3 helicase

Procedia PDF Downloads 208